The glycosaminoglycan interactome: from interactions to functions

Sylvie Ricard-Blum / Université Lyon 1, France

May 27, 2021, 3 - 4 pm (CEST)

Online live talk

Introduction

The six mammalian glycosaminoglycans (GAGs), chondroitin sulfate, dermatan sulfate, heparin, heparan sulfate, hyaluronan, and keratan sulfate, are linear polysaccharides. Except for hyaluronan, they are sulfated to various extent, and covalently attached to proteins to form proteoglycans. GAGs interact with growth factors, morphogens, chemokines, extracellular matrix proteins and their bioactive fragments, receptors, lipoproteins, and pathogens. These interactions mediate their functions, from embryonic development to extracellular matrix assembly and regulation of cell signaling in various physiological and pathological contexts such as angiogenesis, cancer, neurodegenerative diseases, and infections. We have built the first comprehensive draft of the GAG interactome composed of 832 biomolecules (827 proteins and five GAGs) and 932 protein–GAG interactions. This network is a scaffold, which in the future should integrate structures of GAG–protein complexes, quantitative data of the abundance of GAGs in tissues to build tissue-specific interactomes, and GAG interactions with metal ions such as calcium, which plays a major role in the assembly of the extracellular matrix and its interactions with cells. This contextualized interactome will be useful to identify druggable GAG-protein interactions for therapeutic purpose.

Sylvie Ricard-Blum

Sylvie Ricard-Blum received a PhD in Biochemistry (1986) from the University Lyon 1 (France) and worked for 10 years in Pasteur Institute in Lyon on collagen modifications in fibrosis. Then she moved to the Institute of Structural Biology in Grenoble (France) where she started to work on biomolecular interactions involved in the assembly and functions of the extracellular matrix. In 2004 she got a position of full Professor of Biochemistry at the University Lyon 1, where she coordinated the Master programme in Biochemistry (2006-2020). She was deputy director (2013-2019) and is currently director of the Interdisciplinary Sciences - Health doctoral school.

Her work, based on the study of structure - interaction - function relationships of the extracellular matrix, combines biochemistry, biophysics, bioinformatics and systems biology. Her team has developed protein and glycosaminoglycan arrays to screen biomolecular interactions by surface plasmon resonance imaging and has built the extracellular matrix interaction database MatrixDB (http://matrixdb.univ-lyon1.fr/) with a focus on glycosaminoglycans. Her major research interests are multimolecular complexes and interaction networks formed in the pericellular and extracellular matrix and their rewiring in diseases such as Alzheimer’s disease, host-pathogen interactions and cancer. Her team has identified hundreds of interactions involving extracellular matrix proteins and glycosaminoglycans, and has published numerous interaction networks providing new insights in the molecular mechanisms underlying ECM assembly and functions.

She has been Secretary (2001-2007) and President (2008-2012, 2014) of the French Society for Matrix Biology. She serves on the Council of the International Society for Matrix Biology since 2011 and was vice-President (2017-2018), President (2019-2020) and is now Past-President of this society. She is Associate Editor of Matrix Biology and Matrix Biology Plus journals published by Elsevier, editor of the HUPO Proteomics Standard Initiative (HUPO-PSI), and co-chair of the HUPO-PSI Molecular Interactions and PSI-MOD groups.